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Conference Paper: Id-1 promotes angiogenesis in hepatocellular carcinoma through HIF-1α-mediated VEGF upregulation

TitleId-1 promotes angiogenesis in hepatocellular carcinoma through HIF-1α-mediated VEGF upregulation
Authors
Issue Date2006
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
The 97th Annual Meeting of the American Association of Cancer Research (AACR 2006), Washington, DC., 1-5 April 2006. In Cancer Research, 2006, v. 66 n. 8 suppl., p. 438, abstract no. 1860 How to Cite?
AbstractBACKGROUND: Hepatocellular carcinoma (HCC) is a highly vascularized tumor associated with poor prognosis. Angiogenesis plays a critical role in rapid growth and metastasis of HCC. Vascular endothelial growth factor (VEGF) is one of the most important angiogenic factors in HCC. A better understanding of the regulatory mechanisms of VEGF expression in HCC may reveal novel targets for treatment of this cancer. Recently, Id-1 (inhibitor of differentiation/DNA synthesis) has been suggested to play a role in cancer angiogenesis but the molecular mechanism remains unknown. Given the central role of VEGF in cancer angiogenesis, we performed a study to elucidate whether overexpression of Id-1 promotes angiogenesis in HCC by interacting with VEGF. METHODOLOGY: In this study, we examined the expression of Id-1 and its relationship with expression of VEGF in HCC by performing immunohistochemistry on HCC tissue microarray. The role of Id-1 in regulating angiogenesis in HCC was evaluated in vitro by ectopic Id-1 transfection, and the effect of inhibition of Id-1 expression on angiogenesis and tumor growth of HCC was studied in vitro and in vivo. RESULTS: Id-1over-expression correlated with HCC metastasis (p<0.001), and its expression significantly correlated with VEGF expression (p<0.001, r=0.47) by tissue microarray. Ectopic transfection of Id-1 into HCC cell lines induced VEGF secretion, and the culture medium of the Id-1 transfectants could induce morphological change and proliferation of human umbilical vein endothelial cells. Furthermore, the angiogenic effect of the culture medium of the Id-1 transfectants was reversed by treatment with an Flk-1 inhibitor, SU1498, or with a VEGF neutralizing antibody. Id-1 induced transcriptional activation of VEGF by upregulating its promoter harboring hypoxia inducible factor-1α (HIF-1α) binding site. Id-1 was able to increase HIF-1α protein but not mRNA expression. In hypoxic condition, Id-1 increased VEGF expression by stabilizing HIF-1α protein. By anti-sense approach, Id-1 downregulation led to suppression of HIF-1α-mediated VEGF production, and resulted in reduced tumor growth and vascularity when the HCC cells were injected subcutaneously in nude mice. CONCLUSION: Id-1 promoted angiogenesis in HCC through stabilization of HIF-1α protein and increased VEGF expression. Downregulation of Id-1 may be a novel target to inhibit angiogenesis in HCC. ©American Association for Cancer Research
DescriptionSession - Tumor Biology 14: Tumor Angiogenesis and the Microenvironment 2: no. 1860
Persistent Identifierhttp://hdl.handle.net/10722/95069
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorPoon, RTPen_HK
dc.contributor.authorLee, TKWen_HK
dc.contributor.authorYuen, APWen_HK
dc.contributor.authorLing, MTen_HK
dc.contributor.authorWang, XHen_HK
dc.contributor.authorWong, YCen_HK
dc.contributor.authorGuan, XYen_HK
dc.contributor.authorMan, Ken_HK
dc.contributor.authorFan, STen_HK
dc.date.accessioned2010-09-25T15:50:41Z-
dc.date.available2010-09-25T15:50:41Z-
dc.date.issued2006en_HK
dc.identifier.citationThe 97th Annual Meeting of the American Association of Cancer Research (AACR 2006), Washington, DC., 1-5 April 2006. In Cancer Research, 2006, v. 66 n. 8 suppl., p. 438, abstract no. 1860-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/95069-
dc.descriptionSession - Tumor Biology 14: Tumor Angiogenesis and the Microenvironment 2: no. 1860-
dc.description.abstractBACKGROUND: Hepatocellular carcinoma (HCC) is a highly vascularized tumor associated with poor prognosis. Angiogenesis plays a critical role in rapid growth and metastasis of HCC. Vascular endothelial growth factor (VEGF) is one of the most important angiogenic factors in HCC. A better understanding of the regulatory mechanisms of VEGF expression in HCC may reveal novel targets for treatment of this cancer. Recently, Id-1 (inhibitor of differentiation/DNA synthesis) has been suggested to play a role in cancer angiogenesis but the molecular mechanism remains unknown. Given the central role of VEGF in cancer angiogenesis, we performed a study to elucidate whether overexpression of Id-1 promotes angiogenesis in HCC by interacting with VEGF. METHODOLOGY: In this study, we examined the expression of Id-1 and its relationship with expression of VEGF in HCC by performing immunohistochemistry on HCC tissue microarray. The role of Id-1 in regulating angiogenesis in HCC was evaluated in vitro by ectopic Id-1 transfection, and the effect of inhibition of Id-1 expression on angiogenesis and tumor growth of HCC was studied in vitro and in vivo. RESULTS: Id-1over-expression correlated with HCC metastasis (p<0.001), and its expression significantly correlated with VEGF expression (p<0.001, r=0.47) by tissue microarray. Ectopic transfection of Id-1 into HCC cell lines induced VEGF secretion, and the culture medium of the Id-1 transfectants could induce morphological change and proliferation of human umbilical vein endothelial cells. Furthermore, the angiogenic effect of the culture medium of the Id-1 transfectants was reversed by treatment with an Flk-1 inhibitor, SU1498, or with a VEGF neutralizing antibody. Id-1 induced transcriptional activation of VEGF by upregulating its promoter harboring hypoxia inducible factor-1α (HIF-1α) binding site. Id-1 was able to increase HIF-1α protein but not mRNA expression. In hypoxic condition, Id-1 increased VEGF expression by stabilizing HIF-1α protein. By anti-sense approach, Id-1 downregulation led to suppression of HIF-1α-mediated VEGF production, and resulted in reduced tumor growth and vascularity when the HCC cells were injected subcutaneously in nude mice. CONCLUSION: Id-1 promoted angiogenesis in HCC through stabilization of HIF-1α protein and increased VEGF expression. Downregulation of Id-1 may be a novel target to inhibit angiogenesis in HCC. ©American Association for Cancer Research-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/-
dc.relation.ispartofCancer Researchen_HK
dc.titleId-1 promotes angiogenesis in hepatocellular carcinoma through HIF-1α-mediated VEGF upregulationen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailPoon, RTP: poontp@hkucc.hku.hken_HK
dc.identifier.emailLee, TKW: tkwlee@hkucc.hku.hken_HK
dc.identifier.emailYuen, APW: pwyuen@hkucc.hku.hken_HK
dc.identifier.emailLing, MT: patling@HKUCC.hku.hken_HK
dc.identifier.emailWong, YC: ycwong@hkucc.hku.hken_HK
dc.identifier.emailGuan, XY: xyguan@hkucc.hku.hken_HK
dc.identifier.emailMan, K: kwanman@hkucc.hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.identifier.authorityLee, TKW=rp00447en_HK
dc.identifier.authorityLing, MT=rp00449en_HK
dc.identifier.authorityWong, YC=rp00316en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.identifier.authorityMan, K=rp00417en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.identifier.hkuros118595en_HK
dc.identifier.volume66-
dc.identifier.issue8 suppl.-
dc.identifier.spage438, abstract no. 1860-
dc.identifier.epage438, abstract no. 1860-
dc.publisher.placeUnited States-

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